Disruption of prepulse inhibition is associated with compulsive behavior severity and nucleus accumbens dopamine receptor changes in Sapap3 knockout mice.

Obsessive compulsive disorder (OCD) is associated with disruption of sensorimotor gating, which may contribute to difficulties inhibiting intrusive thoughts and compulsive rituals. Neural mechanisms underlying these disturbances are unclear; however, striatal dopamine is implicated in regulation of sensorimotor gating and OCD pathophysiology. The goal of this study was to examine the relationships between sensorimotor gating, compulsive behavior, and striatal dopamine receptor levels in Sapap3 knockout mice (KOs), a widely used preclinical model system for OCD research. We found a trend for disruption of sensorimotor gating in Sapap3-KOs using the translational measure prepulse inhibition (PPI); however, there was significant heterogeneity in both PPI and compulsive grooming in KOs. Disruption of PPI was significantly correlated with a more severe compulsive phenotype. In addition, PPI disruption and compulsive grooming severity were associated with reduced dopamine D1 and D2/3 receptor density in the nucleus accumbens core (NAcC). Compulsive grooming progressively worsened in Sapap3-KOs tested longitudinally, but PPI disruption was first detected in high-grooming KOs at 7 months of age. Through detailed characterization of individual differences in OCD-relevant behavioral and neurochemical measures, our findings suggest that NAcC dopamine receptor changes may be involved in disruption of sensorimotor gating and compulsive behavior relevant to OCD.

Resuscitation Patterns and Massive Transfusion for the Critical Bleeding Dog-A Multicentric Retrospective Study of 69 Cases (2007-2013).

Objective: To describe resuscitation patterns of critically bleeding dogs, including those receiving massive transfusion (MT). Design: Retrospective study from three universities (2007-2013). Animals: Critically bleeding dogs, defined as dogs who received ≥ 25 ml/kg of blood products for treatment of hemorrhagic shock caused by blood loss. Measurements and Main Results: Sixty-nine dogs were included. Sources of critical bleeding were trauma (26.1%), intra/perioperative surgical period (26.1%), miscellaneous (24.6%), and spontaneous hemoabdomen (23.1%). Median (range) age was 7 years (0.5-18). Median body weight was 20 kg (2.6-57). Median pre-transfusion hematocrit, total protein, systolic blood pressure, and lactate were 25% (10-63), 4.1 g/dl (2-7.1), 80 mm Hg (20-181), and 6.4 mmol/L (1.1-18.2), respectively. Median blood product volume administered was 44 ml/kg (25-137.4). Median plasma to red blood cell ratio was 0.8 (0-4), and median non-blood product resuscitation fluid to blood product ratio was 0.5 (0-3.6). MT was given to 47.8% of dogs. Survival rate was 40.6%. The estimated odds of survival were higher by a factor of 1.8 (95% CI: 1.174, 3.094) for a dog with 1 g/dl higher total protein above reference interval and were lower by a factor of 0.6 (95% CI: 0.340, 0.915) per 100% prolongation of partial thromboplastin time above the reference interval. No predictors of MT were identified. Conclusions: Critical bleeding in dogs was associated with a wide range of resuscitation patterns and carries a guarded to poor prognosis.